Chemical investigation of the marine red alga (Rhodophyta) Ceratodictyon spongiosum containing the symbiotic sponge Sigmadocia symbiotica collected from Biaro Island, Indonesia, yielded two isomers of a new and bioactive thiazole-containing cyclic heptapeptide, cis,cis-ceratospongamide (1) and trans, trans-ceratospongamide (2). Isolation of these peptides was assisted by bioassay-guided fractionation using a brine shrimp toxicity assay (Artemia salina). The structures of the ceratospongamides, which each consist of two L-phenylalanine residues, one (L-isoleucine)-L-methyloxazoline residue, one L-proline residue, and one (L-proline)thiazole residue, were established through extensive NMR spectroscopy, including (1)H-(13)C HMQC-TOCSY, and (1)H-(15)N HMBC experiments, as well as chemical degradation and chiral analysis. cis,cis- and trans,trans-ceratospongamide are stable conformational isomers of the two proline amide bonds. Molecular modeling of these two ceratospongamide isomers showed the trans, trans isomer to be quite planar, whereas the cis,cis isomer has a more puckered overall conformation. trans,trans-Ceratospongamide exhibits potent inhibition of sPLA(2) expression in a cell-based model for antiinflammation (ED(50) 32 nM), whereas the cis,cis isomer is inactive. trans,trans-Ceratospongamide was also shown to inhibit the expression of a human-sPLA(2) promoter-based reporter by 90%.

Natural products isolated from marine sponges have exhibited profound bioactivity and, in some cases, serve as potent quorum sensing inhibitory agents by preventing microbial biofilm formation. In this study, the inhibitory potential of the psammaplin type compounds, psammaplin A (1) and bisaprasin (2), isolated from the marine sponge, Aplysinella rhax, was evaluated in the quorum-sensing inhibitory assay based on the Pseudomonas aeruginosa PAO1 lasB-gfp and P. aeruginosa PAO1 rhlA-gfp biosensor strains. The result indicated that psammaplin A (1) showed moderate inhibition against lasB-gfp biosensor strains but significantly inhibited the QS-gene promoters, rhlA-gfp with IC50 value at 30.69 and 2.64 μM, respectively. In contrast, bisaprasin (2) displayed significant inhibition for both biosensor strains, lasB-gfp and rhlA-gfp with IC50 values at 8.70 and 8.53 μM, respectively. To our knowledge, the antiquorum sensing activity of these marine-derived bromotyrosine compounds is described here for the first time.Significance and Impact of the StudyThe attention of the scientific community has been drawn to using marine sources to find novel quorum sensing inhibitors as antipathogenic drugs to combat antimicrobial resistance and pathogenesis caused by the proliferation of pathogenic bacteria mediated by the quorum sensing (QS) system. By blocking the QS signalling communication, the ability to assemble an organised community structure that enables drug resistance and production of virulence factors will be attenuated. The significance of this investigation is based on the discovery of bromotyrosine derivatives as potential new drug leads for the development of antipathogenic agents.